Characterization of the Hemolytic Activity of Mastoparan Family Peptides from Wasp Venoms
Author:
Ye Xiangdong12, Zhang Huajun1, Luo Xudong12, Huang Fengyin3, Sun Fang12, Zhou Liangbin4ORCID, Qin Chenhu12, Ding Li5, Zhou Haimei1, Liu Xin1, Chen Zongyun12
Affiliation:
1. Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, College of Basic Medicine, Hubei University of Medicine, Shiyan 442000, China 2. Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan 442000, China 3. Department of Public Studies, Changde Vocational Technical College, Changde 415000, China 4. Department of Orthopedics and Traumatology, Prince Wales Hospital & Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong 999077, China 5. Department of Clinical Laboratory, Dongfeng Hospital, Hubei University of Medicine, Shiyan 442000, China
Abstract
Biologically active peptides have attracted increasing attention in research on the development of new drugs. Mastoparans, a group of wasp venom linear cationic α-helical peptides, have a variety of biological effects, including mast cell degranulation, activation of protein G, and antimicrobial and anticancer activities. However, the potential hemolytic activity of cationic α-helical peptides greatly limits the clinical applications of mastoparans. Here, we systematically and comprehensively studied the hemolytic activity of mastoparans based on our wasp venom mastoparan family peptide library. The results showed that among 55 mastoparans, 18 had strong hemolytic activity (EC50 ≤ 100 μM), 14 had modest hemolytic activity (100 μM < EC50 ≤ 400 μM) and 23 had little hemolytic activity (EC50 > 400 μM), suggesting functional variation in the molecular diversity of mastoparan family peptides from wasp venom. Based on these data, structure–function relationships were further explored, and, hydrophobicity, but not net charge and amphiphilicity, was found to play a critical role in the hemolytic activity of mastoparans. Combining the reported antimicrobial activity with the present hemolytic activity data, we found that four mastoparan peptides, Parapolybia-MP, Mastoparan-like peptide 12b, Dominulin A and Dominulin B, have promise for applications because of their high antimicrobial activity (MIC ≤ 10 μM) and low hemolytic activity (EC50 ≥ 400 μM). Our research not only identified new leads for the antimicrobial application of mastoparans but also provided a large chemical space to support the molecular design and optimization of mastoparan family peptides with low hemolytic activity regardless of net charge or amphiphilicity.
Funder
National Natural Sciences Foundation of China Foundation of Health Commission of Hubei Province Cultivating Project for Young Scholar at the Hubei University of Medicine Open Project of Hubei Key Laboratory of Wudang Local Chinese Medicine Research
Subject
Health, Toxicology and Mutagenesis,Toxicology
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